Microscopy has played an important role in science and technology. One area where light and electron microscopy techniques have been indispensable is biological sciences. Light microscopy has allowed observation at 200 nanometer (nm) scale resolution, while electron microscopy has demonstrated atomic scale resolution with thin-sectioned specimens. Recent developments in x-ray microscopy have allowed thick hydrated samples with tens of nanometer resolution.
For most effective observations, cells and biological tissues must be imaged in a hydrated state in order to have the highest fidelity representation of the living state. But when imaging hydrated organic specimens using ionizing radiation, radiation damage often limits the quality and resolution of the images that can be obtained. The solution is to work with hydrated specimens that have been rapidly frozen so as to minimize the formation of crystalline ice in the specimens.
Cryogenic specimen handling methods were first developed in electron microscopy in 1974 by K. Taylor and R. Glaeser, see Electron diffraction of frozen, hydrated protein crystals. Science, 106:1036-1037, 1974, and by the late 1980s there was a considerable knowledge base in place regarding rapid freezing and cryo electron microscopy. Cryomicroscopy is also expected to be important in trace element mapping in fluorescence microprobes, since specimen drying is likely to affect the distribution of the diffusible ions that can play such important physiological roles. Cryogenic methods have also found wide spread use in protein crystallography, where the usual practice involves a cryogenic gas stream directed onto a specimen to cool it within an atmospheric pressure, room temperature environment.